Are vancomycin trough concentrations adequate for optimal dosing?

Area of Science:

• Pharmacology
• Infectious Diseases
• Clinical Pharmacy

Background:

• Current vancomycin dosing guidelines for Staphylococcus aureus infections rely solely on trough concentrations.
• Both vancomycin efficacy and toxicity are associated with the area under the plasma concentration-time curve (AUC).

Purpose of the Study:

• To compare AUC estimations from trough-only and full pharmacokinetic data.
• To evaluate the relationship between vancomycin trough concentration and AUC.
• To assess the accuracy of AUC estimation using trough concentrations with and without Bayesian methods.

Main Methods:

• Utilized richly sampled vancomycin pharmacokinetic data from 47 adults.
• Employed Pmetrics, a nonparametric population modeling package for R.
• Compared AUCs from trough-only, peak-trough depleted, and full data models.
• Simulated 5,000 profiles to evaluate therapeutic target achievement.

Main Results:

• Trough-only and peak-trough depleted data sets underestimated true AUCs by 23% and 14%, respectively.
• Using the full model as a Bayesian prior with trough-only data achieved 97% accurate AUC estimation.
• Approximately 60% of adults with normal renal function may have subtherapeutic AUCs despite trough concentrations below 15 mg/L.

Conclusions:

• Vancomycin dose adjustments based solely on trough concentrations without Bayesian tools lead to suboptimal drug exposure.
• Many adults can achieve adequate vancomycin AUC with trough concentrations below 15 mg/L.
• Bayesian analysis is crucial for accurate vancomycin AUC estimation and optimizing therapy.